ID 112459
Author
Iwata, Hiroshi Harvard Medical School
Goettsch, Claudia Harvard Medical School
Sharma, Amitabh Harvard Medical School|Northeastern University
Ricchiuto, Piero Harvard Medical School
Goh, Wilson Wen Bin Harvard Medical School
Halu, Arda Harvard Medical School
Yamada, Iwao Harvard Medical School
Hara, Takuya Harvard Medical School
Wei, Mei Vanderbilt University
Inoue, Noriyuki Harvard Medical School
Mojcher, Alexander Harvard Medical School
Mattson, Peter C. Harvard Medical School
Barabási, Albert-László Harvard Medical School|Northeastern University
Boothby, Mark Vanderbilt University
Aikawa, Elena Harvard Medical School
Singh, Sasha A. Harvard Medical School
Aikawa, Masanori Harvard Medical School
Content Type
Journal Article
Description
Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9–PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.
Journal Title
Nature Communications
ISSN
20411723
NCID
AA12645905
Publisher
Springer Nature
Volume
7
Start Page
12849
Published Date
2016-10-31
Remark
Supplementary Information : ncomms_7_12849_s1.pdf
Rights
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences
Medical Sciences